Persistence of infection with HPV linked to the individual's, and the virus's region of origin

Infection with “high-risk” strains of the genital and anal wart virus (human papilloma virus, or HPV) persists longer in individuals whose racial origin is the same as the region from which the virus originated, according to a US study published in the Journal of the National Cancer Institute. An accompanying editorial praises the study, saying that it will help ensure that the emerging vaccines for HPV will be developed and used appropriately.

Infection with HPV genotypes 16 and 18 have been associated with an increased risk of cancerous and pre-cancerous cell changes in the cervix or anus. Excess rates of HPV infection have been observed in HIV-infected individuals and cervical cancer has been classified as an AIDS-defining illness since 1993.

There are geographical variations between particular HPV genotypes, and it is possible that strains of HPV may have evolved over the centuries to be particularly persistent in people from particular geographic regions. Investigators from the University of Washington therefore conducted a longitudinal study involving 1025 women infected with HPV-16 and/or HPV-18 with low-grade cell changes in the cervix. The investigators looked at the chances of the women clearing infection of the HPV genotype according to their racial origin and the geographic origin of the HPV genotype(s) they were infected with. The women were recruited between early 1997 and the end of 1998 and had cervical specimens collected every six months for two years.

A total of 719 women were white, 251 were African Americans, and 55 were of other racial origin (native American or Asian). Mean age was 25 years. First of all, the investigators looked at what type of HPV-16 and HPV-18 variants women were infected with at baseline.

Variants of HPV-18 were studied in samples from 276 women, and 119 of these samples were strains with a European origin, with African variants present in 79, and Asian in 78. The investigators found that women of African American origin were statistically more likely to be infected with HPV-18 strains of African origin, and that white women were statistically more likely to be infected with strains of the virus of European origin (p < 0.001).

Samples containing HPV-16 were obtained from 719 women, the overwhelming majority containing European variants (82%), with Asian American strains detected in 8% and African and Asian in 1% respectively. African strains of HPV-16 accounted for 27% of the samples obtained from African American women, but only 4% of the samples obtained from white women.

The investigators then looked at the persistence of HPV infection according to the strains’ geographical origin in women of different racial origin.

White women infected with European variants of HPV-18 were statistically more likely to remain infected with this strain of the virus than African American women (p = 0.004). By contrast, African American women were significantly more likely to clear infection with the European variant of HPV-18 than white women (p = 0.03). In addition, the investigators noted that it took women longer to clear infection with HPV-18 strains associated with their area of ancestral racial origin, with white women clearing infection with African strains of HPV-18 in a mean of eleven months and European strains of the virus in a mean of 15 months. African women cleared European variants of HPV-18 in a mean of 13 months and African strains in a mean of 17 months. The likelihood of persistence of HPV-18 variants by racial group was statistically significant (p < 0.001).

Analysis then focused on the persistence of HPV-16 variants. Once again, the investigators found that white women infected with variants of the virus of European origin were statistically more likely to remain infected with that strain of the virus than African American women (p = 0.03). The investigators noted that HPV-16 variants of African origin were 94% more likely to resolve in white women than in African American women (p = 0.014). Once again, time to clearance of the infection was associated with racial origin and the geographical origin of the HPV variant an individual was infected with.

The investigators acknowledge that racial groups may be more likely to “sexually mix” with partners of their own racial group, therefore influencing the variants of HPV an individual becomes infected with. However, they suggest that “genetic factors may predispose women to establish and/or retain infection with particular HPV variants.” The investigators believe that their findings could have implications for HPV treatment and vaccine research and write, “given that women with persistent…HPV-16 or HPV-18 infections are at increased risk of cervical cancer, future studies should be conducted to examine the possible mechanisms involving variant-specific immune evasion and potential clinical and therapeutic implications.”

The authors of the accompanying editorial write, “the implication of these results is that variants of these highly pathogenic types of HPV have coevolved with their host and that coexistence has selected variants with increased duration of infectivity.” They ask if strains of HPV associated with an individual’s area of ancestral origin will continue to evolve and persist, even with the use of HPV vaccines.